DESCRIPTION (Applicant's Abstract): This double-blind, placebo-controlled clinical study will evaluate ritanserin and two manually-guided therapies in the treatment of cocaine dependence. Cocaine dependent patients (N = 198) completing a 14-day inpatient treatment program will be randomly assigned to one of six treatment cells in a 3 X 2 factorial design comparing drug group (placebo, 5 mg, 10 mg) and psychotherapy (relapse prevention, standard drug counseling). The 12-week outpatient treatment will involve twice weekly individual psychotherapy contacts. Relapse prevention techniques will emphasize coping skills training, handling drug use episodes, and general lifestyle changes to maintain abstinence. Standard drug counseling will be nondirective and supportive. Drug history, addiction severity, psychosocial functioning, and coping skills will be measured at pretreatment. During treatment, biweekly urinalysis testing will bs conducted, along with weekly measurement of cocaine craving, side effects, and mood state. Short-term outcome will be assessed at treatment termination, followed by repeated assessments over a 1-year period to examine treatment durability. Primary dependent variables will include cocaine use (urine screen and self-report), treatment attendance, retention rates, and medication compliance. Drug use outcomes will be analyzed according to: (a) proportion of cocaine- positive urine drug screens; (b) duration of continuous periods of abstinence; (c) cocaine craving ratings; (d) rates of relapse to other illicit drugs. Other indices of treatment improvement will include: (a) ASI ratings of problem severity; (b) coping scores on the Situational Competency Test; (c) psychosocial functioning (i.e., depression, social support, perceived stress). We predict that ritanserin will be superior to placebo on outcome measures related to cocaine consumption. Furthermore, type of therapy will interact with the effect of medication on most outcome measures. Specifically, subjects receiving ritanserin and relapse prevention therapy will be less likely to experience a relapse to regular cocaine use and will report better short- and long-term psychosocial functioning compared to subjects in the control groups. Finally, this project will establish a joint pharmacotherapy- psychotherapy model to support research on medications development for cocaine dependence.